The research program of this laboratory deals with the isolation, properties, and biological function of proteins associated with DNA in the chromosomes of higher organisms. Particular emphasis is placed on reactions which modify the structure of nuclear proteins (both histones and non-histone proteins) after their synthesis is completed. Reactions such as acetylation, phosphorylation and methylation of lysine, histidine, serine and threonine residues in the polypeptide chains of DNA-binding proteins are believed to play a role in chromatin assembly and in the control of transciption. The chemical and enzymatic basis of these reactions, and their results in terms of DNA-protein interaction, are a major topic of investigation. Current projects based on this aspect of nuclear protein chemistry deal with; the role of histone structural modifications in the control of chromatin structure, the separation by DNA-affinity chromatography of nuclear proteins which selectively interact with multiple-copy genes, such as ribosomal cistrons, and the characterization of DNA-binding proteins which have high affinities for cyclic AMP or cyclic GMP. Basic knowledge acquired in these studies is being applied to an analysis of changes in nuclear protein composition and metabolism during the cell cycle. Particular emphasis is placed on studies of the selective influx of cytoplasmic alterations in nuclear proteins during early stages of chemically-induced carcinogenesis in the liver and colon.